Ixabepilone: a novel microtubule-stabilizing agent for the treatment of metastatic breast cancer.
OBJECTIVE
The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage, and administration of ixabepilone in patients with metastatic breast cancer are examined.


CONCLUSIONS
The clinical utility of the three main classes of chemotherapeutic agents used in breast cancer (i.e., anthracyclines, taxanes, and fluorinated pyrimidines) is limited in some patients by the emergence of drug resistance which leads to disease progression. A recent addition to the available drugs for the treatment of advanced breast cancer is the epothilone B analog ixabepilone, which has demonstrated clinical activity in patients who have tumors that have progressed while on other chemotherapy regimens, including anthracyclines and taxanes. In Phase II clinical trials of ixabepilone in patients with metastatic breast cancer, clinically meaningful benefits have been achieved with ixabepilone monotherapy in patients in whom anthracyclines, taxanes, and capecitabine are no longer effective. Ixabepilone has demonstrated activity in first-, second-, and subsequent-lines of therapy and in different subtypes of patients with advanced disease. In a Phase III trial in patients who had previously received taxanes and anthracyclines, the combination of ixabepilone and capecitabine was significantly more effective in producing an objective response and in prolonging progression-free survival than capecitabine alone. At the recommended dose and administration schedule, ixabepilone is generally well tolerated. The most clinically relevant adverse events associated with its use have been myelosuppression and peripheral neuropathy, which is primarily sensory and cumulative but reversible within six weeks of a dosage reduction or the discontinuation of therapy.


CONCLUSIONS
Ixabepilone, the first drug in a new class of microtubule-stabilizing agents called epothilones, offers a new treatment option for patients with metastatic or locally advanced breast cancer who are refractory to standard chemotherapy.
Goodin
Susan
S
Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, USA. goodin@umdnj.edu
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D034261:Epothilones / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000639:trends; D050257:Tubulin Modulators / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use
D034261:Epothilones; D050257:Tubulin Modulators; C430592:ixabepilone